Bixin and fuxoxanthin alone and in combination with cisplatin regulate ABCC1 and ABCC2 Transcription in A549 Lung Cancer Cells

Bixin and fuxoxanthin alone and in combination with cisplatin regulate ABCC1 and ABCC2 Transcription in A549 Lung Cancer Cells

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 c...

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Bibliographic Details
Published in:Journal of pharmacy & bioallied science Vol. 15; no. 1; pp. 15 - 20
Main Authors: Chandra, Ferdy, Tania, Teresa, Nurcahyanti, Agustina
Format: Journal Article
Language:English
Published: India Wolters Kluwer India Pvt. Ltd 01-01-2023
Medknow Publications and Media Pvt. Ltd
Medknow Publications & Media Pvt. Ltd
Wolters Kluwer - Medknow
Wolters Kluwer Medknow Publications
Subjects:
a549
ABC transporter
abcc1
abcc2
Antimitotic agents
Antineoplastic agents
Apoptosis
bixin
Carotenoids
Caspase
Cell differentiation
Cell survival
Cisplatin
Drug resistance
Environmental stress
Fucoxanthin
Gene expression
Gene regulation
Genes
Genetic transcription
Lung cancer
Original
p53
p53 Protein
Protein transport
Tumor proteins
Tumor suppressor genes
bixin
ABCC1
ABCC2
carotenoids
A549
cisplatin
fucoxanthin
p53
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Summary: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.
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content type line 23
ISSN:0975-7406
0976-4879
0975-7406
DOI:10.4103/jpbs.jpbs_50_23