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. 2023 Jan-Mar;15(1):15-20.
doi: 10.4103/jpbs.jpbs_50_23. Epub 2023 Apr 14.

Bixin and Fuxoxanthin Alone and in Combination with Cisplatin Regulate ABCC1 and ABCC2 Transcription in A549 Lung Cancer Cells

Ferdy Chandra  1 , Teresa F Tania  1 , Agustina D R Nurcahyanti  1
Affiliations

Bixin and Fuxoxanthin Alone and in Combination with Cisplatin Regulate ABCC1 and ABCC2 Transcription in A549 Lung Cancer Cells

Ferdy Chandra et al. J Pharm Bioallied Sci. 2023 Jan-Mar.

Abstract

Background: The ATP-Binding Cassette (ABC) transporter has long been studied to confer drug resistance in human tumors and play important role in metabolic processes and cellular signaling. The overexpression of ABCB1, ABCC1, ABCC2, ABCC3, and ABCG2 leads to decreased sensitivity of lung cancer to cisplatin. At the transcription level, the expression of ABC transporters is highly regulated and requires the complex interplay of factors involved in differentiation and development, cell survival and apoptosis upon intrinsic and environmental stress. The p53 regulation of drug-resistance genes is also complex yet not well understood. Previously, we demonstrated the synergistic interaction between bixin or fucoxanthin with cisplatin in A549 lung cancer cells.

Objectives: Current study aims to identify whether carotenoids enhancing therapeutic effect of Cisplatin due to the ability to reverse drug resistance associated proteins, such as ABC transporter and regulating the tumor suppressor corresponding gene, p53.

Methods: Real-Time Quantitative-Polymerase Chain Reaction (RT-qPCR) was performed to estimate the expression level of ABCC1 and ABCC2, and p53 of A549 cell lines in response to carotenoids alone and in combination with cisplatin.

Results and conclusion: The administration of bixin or fucoxanthin decreases the expression of ABCC1 and ABCC2. Both carotenoids, either alone or in combination with cisplatin, upregulated p53 gene expression indicating the mechanism of proliferation inhibition and apoptosis occurs via the p53 caspase-independent pathway.

Keywords: A549; ABCC1; ABCC2; bixin; carotenoids; cisplatin; fucoxanthin; p53.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of Bixin, Fucoxanthin, and Cisplatin
Figure 2
Figure 2
Relative Quantification of ABCC1 (left side) and ABCC2 (right side) genes expression of A549 cells treated with Fucoxanthin (Fuc), Bixin (Bix), Cisplatin (Cis), Fucoxanthin and Cisplatin in Combination (Fuc Kom), and Bixin and Cisplatin in Combination (Bix Kom) *indicates a significance difference (P < 0.05)
Figure 3
Figure 3
Relative Quantification of p53 (left side) and caspase 3 (right side) genes expression of A549 cells treated with Fucoxanthin (Fuc), Bixin (Bix), Cisplatin (Cis), Fucoxanthin and Cisplatin in Combination (Fuc Kom), and Bixin and Cisplatin in Combination (Bix Kom) *indicates a significance difference (P < 0.05)
See this image and copyright information in PMC

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