ผลของ astaxanthin จากเปลือกกุ้งขาวต่อการตายของเซลล์มะเร็งปอด A549
Lung cancer is one of the major diseases worldwide, the third leading cause of cancer-related death after breast cancer and prostate cancer. Epidemiological studies have indicated non-small cell lung cancer (NSCLC) to be the predominant type of lung cancer. Current treatments for NSCLC patients are surgery and adjuvant therapy which may include radiation and chemotherapy. Major toxicities including neutropenia, peripheral neuropathy, nausea and vomiting, nephrotoxicity present as major side effects after chemotherapy. Thus, to develop a potent cancer therapeutic agent with low toxicities and fewer side effects would be desirable It has been reported that astaxanthin extracted from the shell of Arabian red shrimp Aristeus alcocki showed a more powerful antioxidant activity than the extract from the green microalgae Haematococcus pluvialis. In addition, free astaxanthin from Litopenaeus vannamei demonstrated a higher percentage of anti-oxidant activity than that from Haematococcus pluvialis. Nevertheless, the potential use of astaxanthin is often limited due to poor water solubility as well as low bioavailability after oral administration and susceptibility to thermal degradation. These obstacles continue to limit on its therapeutic application in aqueous-based system. Thus, the encapsulation of astaxanthin in nanoliposome, whose structure resembles the lipid membrane of living cells, as carrier system would preserve the native properties of astaxanthin as well as provide its stable aqueous dispersion thus improve its therapeutic potential. Therefore, the present study aimed to investigate the in vitro anti-cancer effects of astaxanthin extracted from white shrimp shells Litopenaeus vannamei and encapsulated in liposomes as well as its ability to induce apoptosis and cause cell cycle arrest in human NSCLC A549 cells.
Purpose: To investigate the anti-cancer potential of astaxanthin from Litopenaeus vannamei encapsulated in liposomes (ASX) to treat lung cancer A549 cells.
Methods: Lung adenocarcinoma A549 cells were cultured and treated with ASX, following which cell viability and nuclear staining were performed. Generation of ROS was identified by the DCFH-DA assay while tetramethylrhodamine ethyl ester was used to determine the mitochondrial membrane potential. Flow cytometry was applied to investigate caspase-3/7 activity and cell cycle distribution.
Results: ASX inhibited growth of A549 in a concentration- and time- dependent manner. The IC50 values at 24, 48 and 72 h were 53.73, 22.85, 17.46 µg/mL, respectively (p < 0.05). After incubation with ASX, the morphological changes were observed in A549 cells following Hoechst 33342/PI fluorescent staining. ASX increased ROS generation and was associated with the collapse of mitochondrial membrane potential, which subsequently triggered the activation of caspase-3/7 activity leading to apoptosis (p < 0.05). In addition, A549 cells accumulated in the G0/G1 phase.
Conclusion: The results suggest that ASX is a valuable nutraceutical agent to target A549 lung cancer cells via ROS-dependent pathway as well as blockage of cell cycle progression.
KEYWORDS: Astaxanthin, Litopenaeus vannamei, Lung cancer, A549, Apoptosis
ผู้ให้ข้อมูล: ผู้ช่วยศาสตราจารย์ ดร.มรกต สร้อยระย้า
ชื่ออาจารย์ที่ทำวิจัย: ผู้ช่วยศาสตราจารย์ ดร.มรกต สร้อยระย้า