Effects of Current Chemotherapy Drugs and Natural Agents in Treating Non-Small Cell Lung Cancer

International Journal of Trend in Scientific Research and Development (IJTSRD)
Volume 7 Issue 1, January-February 2023 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470
@ IJTSRD | Unique Paper ID – IJTSRD52646 | Volume – 7 | Issue – 1 | January-February 2023 Page 146
Effects of Current Chemotherapy Drugs and Natural
Agents in Treating Non–Small Cell Lung Cancer
Vaibhav Vikas Sarkate, Miss Puja Vikas Sarkate, Miss Jayshri S. Sanap
Department of Pharmacology, Gawande Collage of Pharmacy, Sakharkherda, Maharashtra, India
ABSTRACT
The fact that lung cancer is the most common cancer to cause death
makes it a desirable condition for study and potential improvement of
therapeutic treatment choices. Lung cancer is frequently treated with
surgery, radiation, chemotherapy, targeted therapies, and
immunotherapy alone or in combination. Chemotherapy-based
regimens appear to have achieved a therapeutic plateau, yet these
treatment modalities may have varied side effects. As a result, this
problem needs to be addressed and hopefully resolved with the help
of efficient, better-tolerated medicines. Recent developments have
made it possible for biologists to more thoroughly explore the
potential application of natural chemicals for the control or therapyof
many malignant conditions. Natural compounds have been the
foundation of chemotherapy for the past 30 years. However, only a
small number of substances have been studied in cancer patients, and
there is only scant information about their clinical efficacy. Here, we
evaluate the evidence for the therapeutic benefits of natural
substances (such as Wortmannin and Roscovitine, Cordyceps
militaris, Resveratrol, OSU03013, Myricetin, Berberine, and
Antroquinonol) and current chemotherapy medicines, including those
against non-small cell lung cancer. We suggest using these medicines
in combination with chemotherapeutic treatments for patients with
advanced and/or refractory solid tumours based on the literature
review.
KEYWORDS: NSCLC; Chemotherapy; Solid tumors; Natural
compounds; Surgery; Radiation
How to cite this paper: Vaibhav Vikas
Sarkate | Miss Puja Vikas Sarkate | Miss
Jayshri S. Sanap "Effects of Current
Chemotherapy Drugs and Natural
Agents in Treating Non–Small Cell
Lung Cancer" Published in International
Journal of Trend in
Scientific Research
and Development
(ijtsrd), ISSN:
2456-6470,
Volume-7 | Issue-1,
February 2023,
pp.146-150, URL:
www.ijtsrd.com/papers/ijtsrd52646.pdf
Copyright © 2023 by author (s) and
International Journal of Trend in
Scientific Research and Development
Journal. This is an
Open Access article
distributed under the
terms of the Creative Commons
Attribution License (CC BY 4.0)
(http://creativecommons.org/licenses/by/4.0)
INTRODUCTION
Lung cancer is the most common cause of death from
cancer overall [1, 2]. It is responsible for 1.4 million
(or 17.7%) of all cancer deaths per year. The most
prevalent form of lung cancer, lung adenocarcinoma,
affects both smokers and nonsmokers as well as
people under the age of 45. About 30% of initial lung
tumours in male smokers and 40% in female smokers
are caused by adenocarcinoma. These figures are
close to 60% for men and 80% for women among
non-smokers. Asian populations are also more likely
to develop this specific type of lung cancer
(www.cancer.gov). In Taiwan, there has been an
increase in the number of lung cancer deaths.
Despite advances in development of new treatment
modalities, the overall 5-year survival rate has only
slightly increased over 2.5 decades, remaining at
approximately 16% [4, 5]. Early diagnostic
procedures and hits, and effective screening for
nonsmall cell lung cancer (NSCLC) is still lacking
[6]. Unfortunately, many patients with lung cancer
are diagnosed at a late stage (i.e. stage III b or IV),
and there is no curative treatment for such an
advanced stage [7]. In Taiwan, liver, lung, stomach,
colon, and oral cavity cancers are the five leading
cancers responsible for cancer deaths among males;
while lung, liver, cervix uteri, breast, and stomach are
the five leading cancers responsible for cancer deaths
among females [8]. Smoking, drinking alcohol, and
chewing betel nut are three significant lifestyle
factors linked to an elevated risk of cancer in Taiwan.
According to a dose-response analysis, smoking
increases the risk of developing lung, hepatoma
cellular carcinoma, oral cavity, neural progenitor
cells, esophageal, urinary bladder, and cervical
cancers [9–12]. Similar to this, tobacco use is one of
the primary etiological factors in western countries,
IJTSRD52646

International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
accounting for 85% of all incidences of lung cancer
[13]. A higher dietary intake of fruits or vegetables is
associated with a lower risk of lung cancer, according
to studies on the role of a person's diet as a potential
risk factor for the disease.
Related Work:
Wang, Kai; Zhang, Chao; Bao, Jiaolin; Jia,
Xuejing; Liang, Yeer; Wang, Xiaotong; Chen,
Meiwan; Su, Huanxing; Li, Peng; Wan, Jian-Bo;
He, Chengwei: Famous natural substances berberine
(BBR) and curcumin (CUR) both display significant
anticancer properties through various molecular
mechanisms. However, neither CUR nor BBR have a
very strong anticancer effect. As a result, we looked
at the chemopreventive potential of combining CUR
and BBR to treat breast cancer. The findings
demonstrated that CUR and BBR reduced the
proliferation of MCF-7 and MDA-MB-231 breast
cancer cells more effectively when used together than
when used separately. Additional research verified
that the co-treatment of these two drugs resulted in
greater levels of apoptosis and autophagic cell death,
which had synergistic anti-breast cancer effects
(ACD). Apoptosis was produced by cotreatment in a
caspase-dependent manner through activating ERK
pathways. Our findings also showed that co-treatment
with CUR and BBR significantly increased JNK and
Beclin 1 phosphorylation while lowering Bcl-2
phosphorylation. JNK inhibition by SP600125
significantly lowered LC3-II and Beclin1, restored
phosphorylated Bcl-2, and lessened the cytotoxicity
brought on by the two substances when used together.
These findings strongly suggested that the co-
administration of CUR and BBR to breast cancer cells
resulted in the production of ACD by the JNK/Bcl-
2/Beclin1 pathway. This research sheds light on how
curcumin and berberine might be used in combination
for the chemoprevention and treatment of breast
cancer.
Po-Cheng Chiang,, Ssu-Chia Lin, Shiow-Lin Pan,
Ching-Hua Kuo, I-Lin Tsai, Mao-Tien Kuo, Wu-
Che Wen, Peini Chen, Jih-Hwa Guh: Two
serine/threonine protein kinases, AMP-activated
protein kinase (AMPK) and mammalian target of
rapamycin (mTOR), are in charge of regulating
translation and maintaining cellular energy balance,
respectively. There is evidence that these two kinases
could be used as cancer treatment targets for
hepatocellular carcinoma (HCC). With regard to both
HBV DNA-positive and -negative HCC cell lines,
antroquinonol, which was extracted from Antrodia
camphorate, a well-known Traditional Chinese
Medicine for the treatment of liver illnesses, shown
potent anticancer activity. HepG2 is the most
effective against HCCs, followed by HepG2.2.15,
Mahlavu, PLC/PRF/5, SK-Hep1, and Hep3B. When
liberated from double-thymidine-block
synchronisation, antroquinonol fully eliminated cell-
cycle progression and triggered apoptosis. The
considerable reversal of antroquinonol-mediated
effects by compound C, a specific AMPK inhibitor,
points to the critical function of AMPK. Additionally,
the reduced mitochondrial content and loss of
mitochondrial membrane potential demonstrated the
mitochondrial stress brought on by antroquinonol. In
conclusion, the evidence indicates that antroquinonol
has anticancer properties against HCCs via activating
AMPK and inhibiting the mTOR translational
pathway, which results in G1 arrest of the cell cycle
and consequent cell apoptosis.
Hsien-Chun Lin, Mei-Hsiang Lin, Jiahn-Haur
Liao, Tzu-Hua Wu, Tzong-Huei Lee, Fwu-Long
Mi, Chi-Hao Wu, Ku-Chung Chen, Chia-Hsiung
Cheng, and Cheng-Wei Lin: The rare fungus
Antrodia camphorata produces antroquinonol, a
ubiquinone derivative with broad-spectrum
bioactivities. However, it is still unknown how ANQ
will affect colon cancer's characteristics resembling
cancer stem cells. In this investigation, we discovered
that ANQ prevented colon cancer cells from growing.
On HCT15 and LoVo, ANQ's 50% growth inhibitory
concentrations (GI50) were 34.8 0.07 M and 17.9
0.07 M, respectively. Additionally, colon cancer cells'
motility, invasion, and creation of tumorspheres were
inhibited by ANQ. A-catenin/T-cell factor (TCF)
signalling was down regulated and pluripotent and
cancer stem cell-related genes were suppressed by
ANQ in a mechanistic manner. Additionally, it was
shown that the phosphatidylinositol-3-kinase
(PI3K)/AKT/-catenin signalling axis is essential for
controlling the expression of pluripotent genes,
whereas ANQ's inhibition of PI3K/AKT suppressed
the production of -catenin and its downstream targets.
The possibility for ANQ and PI3K interaction was
discovered using molecular docking. Using
PI3K/AKT/-catenin signalling as a target, our data
demonstrate for the first time how the bioactive
component of A. camphorata, ANQ, reduces stem
cell-like characteristics. An effective cancer
preventative for colon cancer may be ANQ.
Zhi Hong Wanga, Kyoung Ah Kanga, Rui
Zhanga, Mei Jing Piaoa, Su Hyun Jo b, Ju Sun
Kimc, Sam Sik Kangc, Jong Sung Lee d, Deok
Hoon Park d, Jin Won Hyuna: By measuring the
scavenging power of reactive oxygen species (ROS)
and the activities of antioxidant enzymes, we assessed
the cytoprotective impact of myricetin on cells
injured by oxidative stress. Myricetin demonstrated

the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals'
ability to scavenge intracellular ROS. Myricetin also
reversed the effects of hydrogen peroxide (H2O2) on
cellular antioxidant defence enzymes such superoxide
dismutase (SOD), catalase (CAT), and glutathione
peroxidase (GPx), restoring their activity and protein
expression. Myricetin was discovered to prevent the
DNA damage indicated by suppression of DNA tail
and it decreased nuclear phospho-histone H2A.X
expression, both of which are markers for DNA
strand breakage. H2O2-induced cellular DNA and
lipid damages were also observed. Additionally,
membrane lipid peroxidation was reduced, as
evidenced by the reduction of TBARS production and
diphenyl-1-pyrenylphosphine fluorescence intensity
(DPPP). These findings imply that myricetin protects
cells from H2O2-induced cell damage by preventing
the production of ROS and stimulating the activity of
antioxidant enzymes.
TAO ZHANG, GUANG-BIN CUI, JIAN ZHANG,
FENG ZHANG, YONG-AN ZHOU, TAO JIANG
and XIAO-FEI LI: Ionizing radiation is not as
damaging to non-small cell lung cancer (NSCLC)
cells as it is to other cancers (IR). The
phosphatidylinositol 3-kinase (PI3-K) family of lipid
kinases mediates biological processes such cell
growth, proliferation, and DNA repair, all of which
may aid in radioresistance. We investigated if PI3
kinase inhibition could improve NSCLC cell
sensitivity to radiation. The findings demonstrated
that wortmannin, a PI3 kinase inhibitor, pretreated
NSCLC A549 and H1650 cells in a dose-dependent
manner that increased G2/M arrest and death, hence
reducing colony formation and radiosensitizing the
cells. Increased loss of mitochondrial membrane
potential (MMP) and cytochrome c leakage to the
cytoplasm were seen in conjunction with the
accelerated apoptosis. . Additionally, pretreatment
with wortmannin markedly boosted caspase-3
activation, which was connected to the suppression of
the X-linked inhibitor of apoptosis protein (XIAP).
Wortmannin's radio sensitizing action and the level of
phosphorylated PKB/Akt were both inhibited.
Additionally, wortmannin decreased the activity of
DNA-PKcs, a component of DNA double-strand
break (DSB) repair, down-regulating its expression.
This prevented DSBs from rejoining, as seen by an
increase in the amount of -H2AX 24 hours after IR.
Together, these findings show that wortmannin
inhibits DNA-PKcs and PI3K/Akt survival signalling
in NSCLC cells, acting as a potent radio sensitizer.
These findings raise the possibility that PI3 kinase
inhibitors may be a new means of overcoming
NSCLC cells' resistance to IR-induced apoptosis.
Soo-Yeon Park, Young Mee Kim, Hongryull
Pyo: A subgroup of patients with non-small cell
lung cancer (NSCLC) treated with EGFR
inhibitors experienced remarkable improvements,
and they have also been proven to improve the
effects of ionising radiation (IR).We looked into
the radio sensitization of NSCLC cells caused by
the EGFR inhibitor gefitinib, which is taken
orally by NSCLC patients.NCI-H460 and
VMRC-LCD but not A549 cells were radio
sensitized by gefitinib in clonogenic survival
experiments carried out in three NSCLC cell
lines. NCI-H460 and VMRC-LCD cells were
exposed to IR following gefitinib pretreatment,
whereas A549 cells were not. Additionally,
gefitinib prevented, but did not stop, the
activation of ataxia telangiectasia mutant (ATM)
after IR exposure in NCI-H460 and VMRC-LCD
cells. In both NCI-H460 and A549 cells, an
ATM-specific inhibitor enhanced the number of
multinucleated cells brought on by IR.
Pretreatment with gefitinib prevented NCI-H460
but not A549 cells from gradually losing gH2AX
foci in relation to time following IR exposure.
After receiving gefitinib + IR treatment, COX-2
suppression in A549 cells led to multinucleated
cells and radio sensitization. On the other hand,
after the same treatment, COX-2 overexpression
in NCI-H460 cells reduced the development of
multinucleation and radio sensitization. Our
findings imply that gefitinib radio sensitizes
NSCLC cells by preventing ATM activity and
thus triggering mitotic cell death, and that
gefitinib is inhibited by COX-2 overexpression in
NSCLC cells.
W. L. Wendy Hsiao, Liang Liu: Herbal remedies
based on traditional Chinese medicine have become
more widely accepted in recent years, and
pharmaceutical companies are pursuing them as
valuable sources for new medication development.
Traditional Chinese medicine (TCM) has been used
for many years in China and other countries to treat
malignancies. Herbal medications are typically
inexpensive, readily available, and exhibit relatively
minimal toxicity or adverse effects in therapeutic
settings. The biggest barriers to the globalisation of
TCM, despite the enormous interest and rising
demand, are the lack of good evidence-based research
and the lack of standardisation of herbal products. As
analytical tools and procedures have advanced
recently, TCM research has greatly increased. This
analysis of TCM's application in the treatment of
cancer is broken up into two sections. The first
section gives an overview of the principles, methods,
and developments in TCM-based cancer therapy. The

second section outlines what is known currently about
how TCM-derived substances work as anticancer
medications.
Alan L. Harvey, Ian A. Cree: The majority of
anticancer medications have been derived from
natural products, and attempts are still being made to
discover new lead compounds by examining the
chemical diversity that nature provides. High
throughput screening assays have evolved from
bioassay test procedures employing both cell-based
and molecular techniques. Examples of recent
breakthroughs using three-dimensional cultures and
cancer stem cells are shown, along with a summary of
the many methods for detecting impacts on cell
survival and proliferation. The development of cell-
based reporter assays has also allowed for a more
direct examination of the impact on particular
physiological pathways. Several distinct protein
kinases as well as microtubules and associated
proteins are the targets of the molecular assays.
Zhi Hong Wanga, Kyoung Ah Kanga, Rui
Hoon Park d, Jin Won Hyun: By measuring the
scavenging power of reactive oxygen species (ROS)
and the activities of antioxidant enzymes, we assessed
the cytoprotective impact of myricetin on cells
injured by oxidative stress. Myricetin demonstrated
the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals'
ability to scavenge intracellular ROS. Myricetin also
reversed the effects of hydrogen peroxide (H2O2) on
cellular antioxidant defence enzymes such superoxide
dismutase (SOD), catalase (CAT), and glutathione
peroxidase (GPx), restoring their activity and protein
expression. Myricetin was discovered to prevent the
DNA damage indicated by suppression of DNA tail
and it decreased nuclear phospho-histone H2A.X
expression, both of which are markers for DNA
strand breakage. H2O2-induced cellular DNA and
lipid damages were also observed. Additionally,
TBARS production and fluorescence intensity of
membrane lipid peroxidation were inhibited.
Chia-Chun Yua, Po-Cheng Chianga, Pin-Hsuan
Lua, Mao-Tien Kuob, Wu-Che Wenb, Peini
Chenc, Jih-Hwa Guha: A malignant pancreatic
tumour is called pancreatic cancer. In more than 90%
of pancreatic adenocarcinomas, K-ras has a mutation
and is constitutively activated. It is critical to find an
effective strategy for the treatment of pancreatic
malignancies. An isolated ubiquinone derivative from
a camphor tree is called antroquinonol. On the other
hand, K-ras expression and phosphorylation both
considerably increased. The oimmunoprecipitation
experiment revealed a markedly increased connection
between K-ras and Bcl-xL, which was suggestive of
apoptotic cell death. In addition, apoptosis,
autophagic cell death, and accelerated senescence
were all brought on by antroquinonol, which was at
least partially explained by the up-regulation of
p21Waf1/Cip1 and K-ras. In conclusion, the evidence
points to the possibility that antroquinonol causes
anticancer activity in human pancreatic tumours via
inhibiting the PI3-kinase/Akt/mTOR pathways, which
in turn suppresses cell cycle egulators.p21Waf1/Cip1
and K-ras were upregulated, which, at least in part,
accounted for the observed phenomenon. In
conclusion, the evidence points to the possibility that
antroquinonol causes anticancer activity in human
pancreatic tumours via inhibiting the PI3-
kinase/Akt/mTOR pathways, which in turn
suppresses cell cycle regulators. The cell cycle is
stopped in the G1 phase due to the translational
inhibition, which leads to a mitochondrial-dependent
death. Additionally, the anticancer effect of
antroquinonol is also explained by autophagic cell
death and hastened senescence.
Existing System/Open Issues:
Recent developments have made it possible for
biologists to more thoroughly explore the potential
application of natural chemicals for the control or
therapy of many malignant conditions. Natural
compounds have been the foundation of
chemotherapy for the past 30 years. However, only a
small number of substances have been studied in
cancer patients, and there is only scant information
about their clinical efficacy. Here, we evaluate the
evidence for the therapeutic benefits of natural
substances (such as Wortmannin and Roscovitine,
Cordyceps militaris, Resveratrol, OSU03013,
Myricetin, Berberine, and Antroquinonol) and current
chemotherapy medicines, including those against
non-small cell lung cancer.
Negative comments:
Peripheral neuropathy or other nerve problems, such
as numbness, tingling, and pain. Skin and nail
changes such as dry skin and color change. Urine and
bladder changes and kidney problems.
The toxic side effects, the development of resistance
to the chemical agents, and the need for other forms
of treatment, in combination with chemotherapy, in
order to cure the patient.
Mouth, tongue, and throat problems such as sores and
pain with swallowing.
Conclusion:
Patients with NSCLC in the early stages often have
two treatment options: surgery or radiotherapy.
Chemotherapy has demonstrated some efficacy when

administered alone to individuals with stage IV
illness, as well as when combined with radiotherapy
to treat patients with locally progressed disease and
those with early-stage NSCLC prior to surgery. Based
on clinical research and the findings of meta-analyses,
platinum medicines are still regarded as being of
utmost importance, despite their documented toxicity
and inherent resistance. Chemotherapy's poor efficacy
and significant toxicity have led to a lot of scepticism
about this strategy for a long time because just a
minor improvement in survival rates was noticed.
Natural substances, meantime, have been utilised to
treat a variety of illnesses and are expanding as a key
field of study for the development of new drugs. It
may be feasible to control and manage cancer by
combining natural medicines with chemotherapy
drugs in patients with advanced and/or refractory
solid tumours. This would lower the toxicity risk
brought on by chemotherapy.
REFERENCES:
[1] Wang, Kai; Zhang, Chao; Bao, Jiaolin; Jia,
Xuejing; Liang, Yeer; Wang, Xiaotong; Chen,
Meiwan; Su, Huanxing; Li, Peng; Wan, Jian-
Bo; He, Chengwei: Synergistic
chemopreventive effects of curcumin and
berberine on human breast cancer cells through
induction of apoptosis and autophagic cell
death. IEEE, 2017.
[2] Po-Cheng Chiang, Ssu-Chia Lin, Shiow-Lin
Pan, Ching-Hua Kuo, I-Lin Tsai, Mao-Tien
Kuo, Wu-Che Wen, Peini Chen, Jih-Hwa Guh:
Antroquinonol displays anticancer potential
against human hepatocellular carcinoma cells:
A crucial role of AMPK and mTOR pathways,
IEEE, 2010.
[3] Hsien-Chun Lin, Mei-Hsiang Lin, Jiahn-Haur
Liao, Tzu-Hua Wu, Tzong-Huei Lee, Fwu-
Long Mi, Chi-Hao Wu, Ku-Chung Chen, Chia-
Hsiung Cheng, and Cheng-Wei Lin:
Antroquinonol, a Ubiquinone Derivative from
the Mushroom Antrodia camphorata, Inhibits
Colon Cancer Stem Cell-like Properties:
Insights into the Molecular Mechanism and
Inhibitory Targets, IEEE, 2016.
[4] Zhi Hong Wanga, Kyoung Ah Kanga, Rui
Hoon Park d, Jin Won Hyuna: Myricetin
suppresses oxidative stress-induced cell
damage via both direct and indirect antioxidant
action, IEEE, 2010.
[5] TAO ZHANG, GUANG-BIN CUI, JIAN
ZHANG, FENG ZHANG, YONG-AN ZHOU,
TAO JIANG and XIAO-FEI LI: Inhibition of
PI3 kinases enhances the sensitivity of non-
small cell lung cancer cells to ionizing
radiation, IEEE, 2010.
[6] Soo-Yeon Park, Young Mee Kim, Hongryull
Pyo: Gefitinib radiosensitizes non-small cell
lung cancer cells through inhibition of ataxia
telangiectasia mutated, IEEE, 2010.
[7] W. L. Wendy Hsiao, Liang Liu: The Role of
Traditional Chinese Herbal Medicines in
Cancer Therapy – from TCM Theory to
Mechanistic Insights, IEEE, 2010.
[8] Alan L. Harvey, Ian A. Cree: High-Throughput
Screening of Natural Products for Cancer
Therapy, IEEE, 2010.
[9] Zhi Hong Wanga, Kyoung Ah Kanga, Rui
Hoon Park d, Jin Won Hyun: Myricetin
suppresses oxidative stress-induced cell
damage via both direct and indirect antioxidant
action, IEEE, 2010.
[10] Chia-Chun Yua, Po-Cheng Chianga, Pin-Hsuan
Lua, Mao-Tien Kuob, Wu-Che Wenb, Peini
Chenc, Jih-Hwa Guha: Antroquinonol, a natural
ubiquinone derivative, induces a cross talk
between apoptosis, autophagy and senescence
in human pancreatic carcinoma cells, IEEE,
2012.

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