September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effects of Anticancer Drug Cisplatin on Cybrids Containing A, B, D or L Haplogroup mtDNA
Author Affiliations & Notes
  • Gregory Yung
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Kunal Thaker
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Marilyn Chwa
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Sina Abedi
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Tej Patel
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Theresa Thai
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Cristina M Kenney
    Gavin Herbert Eye Institute-UCI, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Gregory Yung, None; Kunal Thaker, None; Marilyn Chwa, None; Sina Abedi, None; Tej Patel, None; Theresa Thai, None; Cristina Kenney, None
  • Footnotes
    Support  Discovery Eye Foundation, Guenther Foundation, Beckman Initiative for Macular Research, Polly and Michael Smith Foundation, Max Factor Family Foundation, Iris and B. Gerald Cantor Foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6052. doi:
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      Gregory Yung, Kunal Thaker, Marilyn Chwa, Sina Abedi, Tej Patel, Theresa Thai, Cristina M Kenney; Effects of Anticancer Drug Cisplatin on Cybrids Containing A, B, D or L Haplogroup mtDNA. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6052.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Mitochondria (mt) DNA can be categorized into haplogroups according to the accumulation of single nucleic polymorphisms (SNPs). While the influence of mitochondria in metabolism has been established, the extent to which mtDNA haplogroups influence intercellular metabolic activities is not well understood. It is recognized that different racial/ethnic populations have different susceptibilities to diseases and responses to medication. The present study characterizes the response of transmitochondrial cybrids containing either A (non-white Hispanic, B (non-white Hispanic), D (East Asian) and L (African origin) haplogroups to Cisplatin, a commonly used cancer drug.

Methods : Cybrids were created by fusing platelets from donors with different ethnic/racial backgrounds with Rho0 ARPE-19 cells (lacking mtDNA). Cybrids containing either A (n=2), B (n=2), D (n=3), or L(n=5) haplogroups were treated with 40 µM Cisplatin for 48 hours and then cell viabilities were measured with the MTT assay. Data were calculated based upon 6-12 wells per cell line. The untreated cybrid values were normalized to 100% to serve as the baseline. An unpaired t-test was used to analyze the data (GraphPad Prism 5).

Results : The L cybrids showed significantly reduced viability between Untreated cybrids (100% ± 5.42) and Cisplatin-treated groups (69.75 ± 5.81%, p = 0.0003). D cybrids had decreased cell viability after Cisplatin treatment (77.39 ± 2.13%, p < 0.0001) compared to Untreated D cybrids (100% ± 1.58). The A cybrids also showed lower cell viability (80.11 ± 3.75%) compared to Untreated A cybrids (100% ± 3.83, p = 0.0007). In contrast, Cisplatin-treated B cybrids had similar levels of cell viability compared to Untreated B cybrids (95.27 ± 4.96% versus 100% ± 8.09, p = 0.62).

Conclusions : Our results show the degree of cytotoxic effects of Cisplatin can vary depending upon the mtDNA haplogroup contained within the cells; L (African origin) cybrids > D (Asian origin) cybrids > A (non-white Hispanic) cybrids > B (non-white Hispanic) cybrids. These data suggest an individual’s mtDNA background may play a greater role than previously thought in responses and side effects to Cisplatin and may redefine the appropriate anticancer treatment and chemotherapy for different racial groups.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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