Melatonin potentiates cisplatin‐induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells

Abstract

These data demonstrate that melatonin enhanced cisplatin-induced cytotoxicity and apoptosis in SK-LU-1 lung cancer cells. SK-LU-1 cell population growth inhibition was mediated by cell cycle arrest in the S phase. These findings suggest that melatonin has the potential to be used for NSCLC treatment in combination with a chemotherapeutic agent such as cisplatin.

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

“…Apoptosis is a well-known mechanism of programmed cell death that does not injure normal neighboring cells and reduces local inflammation [74]. Since programmed cell death by apoptosis serves as a natural barrier to cancer development [73], apoptotic induction is an important mechanism initiated by chemotherapeutic agents [5]. Melatonin exerts anti-apoptotic effects in normal cells exposed to toxic agents or metabolic injury.…”

“…Surgery and chemoradiotherapy are the two major treatments to prolong the survival of NSCLC patients, but improvements are marginally effective [4]. Moreover, radio- or chemotherapies often lead to undesirable side effects on normal cells or tissues, which limits their use as a treatment for cancer [5]. Thus, a number of studies were devoted to overcoming the deleterious effects and enhancing the efficacy of these treatments when given in combination with the appropriate supplement such as melatonin, which is well known lack of toxic and undesirable side effects [5–8].…”

“…As a potent free radical scavenger and antioxidant, melatonin has the capacity to scavenge up to 10 reactive oxygen species (ROS) via the cascade reaction means, which distinguishes melatonin from the classic antioxidants that scavenge only one or less ROS [11–13]. Additionally, numerous publications have reported that melatonin inhibits the growth of a variety of cancers: lung [5, 14, 15], breast [16–20], prostate [21–24], liver [25, 26], colon [27, 28], etc. The oncostatic mechanisms of melatonin are related to several hallmarks of cancer, including anti-proliferation [14], induction of apoptosis [5, 14, 15], inhibition of invasion and metastasis [29, 30], anti-angiogenesis [16, 31], and enhancement of immunomodulation [32] among others.…”

“…Additionally, numerous publications have reported that melatonin inhibits the growth of a variety of cancers: lung [5, 14, 15], breast [16–20], prostate [21–24], liver [25, 26], colon [27, 28], etc. The oncostatic mechanisms of melatonin are related to several hallmarks of cancer, including anti-proliferation [14], induction of apoptosis [5, 14, 15], inhibition of invasion and metastasis [29, 30], anti-angiogenesis [16, 31], and enhancement of immunomodulation [32] among others. Furthermore, clinical studies have demonstrated that melatonin treatment enhances the efficacy and reduces the side-effects of chemotherapy, prolongs survival time, and improves quality of life for NSCLC patients [8, 33].…”

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells

“…Melatonin has also been shown to exert antiproliferative and cytotoxic effects on human cancers, including colorectal cancer [7], neuroblastoma [8], hepatocarcinoma [9], lung cancer [10-12], breast cancer [13], prostate cancer [14, 15], and leukaemia [16, 17]. In a gastric cancer cell line it was already shown that proapoptotic effect of melatonin could be due to activation of a Caspase-dependent pathway and inhibition of the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and c-Jun N-terminal kinase (JNK) [18].…”