Cucurbitacin B Inhibits Non Small Lung Cancer Cells in Vitro and Vivo

By Kyle J. Norton

Lung cancer is a medical condition caused abnormal growth of the cells in the lung’s tissue. Most common form of primary lung cancers is derived from epithelial cells.
Non-small lung cancer is the most common type of lung cancer that accounts for 80% to 85% of all cases of lung cancers, usually grows and spreads methodically and predictably.

Most common types of lung cancers include
*  Squamous-cell carcinoma often found in an outer area of the lung

* Large-cell carcinoma found in the center of the lung by an air tube

* Adenocarcinoma found in any part of the lung.

According to the statistics provided by the American cancer society, lung cancer is a leading cause of death among both men and women. Most people diagnosed with lung cancer are 65 or older, compared to a very small number of people diagnosed are younger than 45.

Most common prevalent factors of non-small cell lung cancer include

1. Smoking
Smoking is a major cause of lung cancer by enhancing oxidation stress by combining the inhaling air  with cancer-causing chemical substances (carcinogens) in the cigarette.
 Normally, our body can withstand and repair this damage, but prolonged exposure your lung to these danger carcinogens can result in lung cancer development.

2. Second-hand smoke
Prolonged exposure to second-hand smoke can also increase the risk of lung cancer.

3. Exposure to certain chemicals
There is an increased risk of lung cancer for people who inhale or exposing certain industrial chemical such as radon gas, arsenic, chromium, nickel, etc. in the workplace.

4. Family history
Risk of lung cancer increased if one of the members of your direct family has lung cancer.

5. Lung disease
Risk of ling can caner increase if you have or previously had certain types of lung disease

6. Excessive drinking
According to the study by Freudenheim et al., R. Curtis Ellison MD suggested that alcohol intake of more than 2 drinks per day is associated with a small increased risk of lung cancer. This study, like others, suggests a weak, positive association between consuming larger amounts of alcohol (>2 drinks a day) and lung cancer risk.

Out of many risk factors, some researchers aging may be one of the major condition as most patients with lung cancer was diagnosed with the age of 65 and over.

Dr. Federico Venuta, the lead researcher wrote, “The respiratory system undergoes a number of structural, physiological and immunological changes with age. For this reason, at this stage of our life, it is not always easy to differentiate disease from a normal state”.

And, “From the epidemiological point of view, early-stage lung cancer is observed more frequently in elderly patients; in fact, stage I disease increases from 79% in patients younger than 65 years to 87% in those above 75 years (25). Also, resectability obviously increases with age (1,26): from 15.3% in those younger than 54 years to 25% above 75 years”.

The cucumber plant is a species of Cucumis Sativus, belongings to the family Cucurbitaceae and native to Western Asia. It is a creeping vine with roots in the ground and grows up with the support of frames.

With an aim to find a natural and potential compound for the treatment of non-small lung cancer (NSCLC) with no side effects, researchers investigated Cucurbitacin B (CuB), a natural compound isolated from cucumber and other vegetables anti-NSCLC in vitro.

Four NSCLC cells (H1299, A549, HCC-827, and H661) in vitro and the highly aggressive H1299 xenograft in vivo were included in the study.

According to the tested assays, CuB significantly induced G2/M cell-cycle arrest and mitochondrial apoptosis.

Injection by the thiol antioxidant N-acetylcysteine (NAC) in the experiment showed to attenuate all cellular effects of CuB completely.

Interestingly, pretreatment with glutathione synthesis inhibitor butithione-sulfoxime (BSO), significantly exacerbated CuB’s cytotoxic effects against the tested cancer cells in both vitro and vivo.

Further analysis of the anti-NSCLC efficacy of CuB, researchers found that CuB induces cell death via rapidly and significantly decrease the levels of protein thiols and GSH/GSSG ratio by disrupting cellular redox balance induced cytotoxicity.

Dr. Kausar H, the lead scientist said, “CuB interacts with and modulates cellular thiols to mediate its anti-cancer effects. Collectively, our data shed new light on the working mechanisms of CuB and demonstrate its therapeutic potential against NSCLC”.

Furthermore, CuB also exerted anti-NSCLC in vitro and vivo CuB by exhibiting a strong anti-migratory and anti-invasive ability against metastatic NSCLC at nanomolar concentrations.
In other words, CuB showed significant tumor angiogenesis-inhibitory effects by the inhibition of migratory, invasive and tube-forming capacities of human umbilical vein endothelial cells.

Moreover, in experimental EMT model CuB also suppressed the overexpression of protein associated with the production of proinflammatory cytokines in the initiation of cellular change and Wnt/β-catenin signaling axis in stimulating the production of formation of new blood vessels to facilitate cancer proliferation.

Taken altogether, cucumber processed a high amount of CuB may be considered supplements for the prevention and treatment of non-small cell lung cancer, pending to the confirmation of the larger sample size and multicenter human study.

Intake of CuB in the form of supplement should be taken with extreme care to prevent overdose acute liver toxicity.
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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it’s news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Named 50 of the best health Tweeters Canada – Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

(1) Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets by Kausar H1, Munagala R, Bansal SS, Aqil F, Vadhanam MV, Gupta RC. (PubMed)
(2) Cucurbitacin B inhibits the stemness and metastatic abilities of NSCLC via downregulation of canonical Wnt/β-catenin signaling axis by Shukla S1, Sinha S1, Khan S1, Kumar S2, Singh K3, Mitra K3, Maurya R2, Meeran SM. (PubMed)
(3) Lung cancer in elderly patients by Federico Venuta, Daniele Diso, Ilaria Onorati, Marco Anile, Sara Mantovani, and Erino A. Rendina. (PMC)