Antitumor Potential of Annona muricata Linn. An Edible and Medicinal Plant in Mexico: In Vitro, In Vivo, and Toxicological Studies.

Verenice Merlín-Lucas,Aida Solís,Elizabeth Barbosa,Normand García-Hernández,Fernando Calzada,Miguel Valdés,Rosa María Ordoñez-Razo

doi:10.3390/molecules26247675

Abstract

Annona muricata (Am) is a plant used in traditional Mexican medicine to treat cancer. In this study, ethanol extracts of Am collected in Acapulco and Tecpan from Guerrero state were evaluated orally on Balb/c mice inoculated with 4T1 cells, for cytotoxic activity (CA) on 4T1 cells, in brine shrimp lethality assay (BSLA), and for acute oral toxicity in mice. In addition, ethanol extracts were subjected to high-performance liquid chromatography (HPLC) with diode array detection. Results showed that the extracts collected in December in Acapulco (AcDe) and Tecpan (TeDe) exhibited the most significant antitumor and cytotoxic activity. In the BSLA, the most important effect was observed in the extracts from Acapulco and Tecpan collected in June (AcJu) and August (TeAg), respectively. The samples from Acapulco (AcJu, and AcAg) and Tecpan (TeJu and TeAg) showed the highest toxicity. The analysis of the extracts, AcDe and TeDe, by HPLC revealed that flavonoids, rutin, narcissin, and nicotinflorin were the major components. These findings suggest that extracts from Am collected in Acapulco and Tecpan in the month of December may be an important source to obtain flavonoid glycosides with anticancer potential specifically against breast cancer. This also supports the use of Am to treat cancer in Mexican traditional medicine.

Highlights

Cancer encompasses a large group of diseases characterized by the development of abnormal cells, which divide and grow uncontrollably in any part of the body [1]; it is considered one of the major contributors to premature mortality around the world
The results showed that best yields of the extract were obtained in April from samples collected in Acapulco and Tecpan de Galeana
The anticancer potential was evaluated using in vivo and in vitro assays, including cytotoxic activity on 4T1 cells, the breast cancer model in Balb/c female mice inoculated with 4T1 cells, brine shrimp lethality assay (BSLA), and acute oral toxicity

Summary

Introduction

Cancer encompasses a large group of diseases characterized by the development of abnormal cells, which divide and grow uncontrollably in any part of the body [1]; it is considered one of the major contributors to premature mortality around the world. It is expected that the global number of cancer patients will increase in the 50 years due to demographic changes such as population growth and aging [2]. In this sense, breast cancer has been one of the most prevalent and the most common cancers in women around the world, and in Mexico, with approximately 2.2 million cases in 2020, becoming the leading cause of mortality [3,4]. Chemotherapy, radiotherapy, and surgery are currently essential therapeutic tools used for breast cancer; these treatments are associated with adverse side effects in women as well as their high cost, especially in developing countries. 2 of 15 2 of 14 are associated with adverse side effects in women as well as their high cost, especially in Adseaverleospuilntg, pceooupnlteridesia. gAnsoaserdeswulitt,hpceaonpclerdaiaregnloosekdinwgittoh ncantucrearlapreroldouokcitnsgobtotaninaetudrafrlom mperdodicuinctaslopbltaanintsetdofcroommpmleemdiecnintatlhpeliarnttrseatotmcoemntps.leImn ethntisthceoinrtterxeta,ttmheenstcsi.eInntitfihcisccoomntmexut,nity isthine csrceiaesnitnifgiclycionmtemreusnteitdy iins minocrreeaesfifnegcltyivien,telersesstheadrminfumlo, raendefnfeocvtievlen, aletussrahlaarlmtefrunl,atainvdes. noveIlnnMatuexraicl oa,ltemrnoarteivtehsa. n 90% of the population uses medicinal plants to treat their diseasInesM, aenxidcob, emtworeeetnha3n09a0n%do7f 0th%e poof pcualnactieornpuasteisenmtsedairceinwaliplllianngtsttoo utrseeatatnhyeirpdroisd-uct oebatsaeins,eadnfdrobmetwtheeenm3e0daicninda7l0p%laonftccaonncseirdperaitniegntths aatrethweyillpinegrcteoivuesethaensyeparsoedfufeccttoivbetaainndedsafe dfuroemtoththeemirendaictiunraallpolraingtinco[n5s]i.dMereinxgictohiast athceoyupnetrrcyeiwveitthhaesgeraesaet fafebcutnivdeaanncde saanfeddduiveetorsity otfhneiartunaratul rparloodriugcints[t5h].aMt mexaiycobies aa cpooutnetnrtyiawl istohuarcgerefaotratbhuenddiasnccoevaenryd odfivceormsitpyooufnndastuw- ith thraelrapproeduuticctsapthpalticmataiyonbse[a6]p. oIttehnatisabl eseonurdceesfcorribtheed dthisactoavbeoryuto6f 0c%omopfotuhneddsrwugitshatphperrao-ved wftrooooetpcsi[dnfnh7ieasreidect]saeonu.MhcateroucrbatTnecleiiferyenhcbhcrcxstsceueehdfhaeiteorctspaeaikmerors[rvpindb7thcnmaeelro]ehiadnii.cwMetsnbvhiaTdtficunetoemtekiihirtci,nroxtenorepicahnindpmooocolmseaiwormricuielit[nregaaad6npsmdlioen]ntl,in.arsicaertccoiniIriniosmoingtncptdnomfisiahiamupanclsttalmlrhhoauiespiczulearndbeeelbttsaartiadAmefrcechnnno,oeiisnadntaeratnpvsnoaldnsiosieolfdctzodiubhanpcateeutblhiwanasldanratcrectitc,rinaenriedoeh-aiAgltaicbepsnnaifeapne.ologdvinydlTcnnfraecaapwhssonetomlt.oaehnrutibrAtrndsaiapeedetl.tt.eaycngriiiTlemeioa-tsiyncwidoabphauaaienoseelenrsnltursirrpaafgucct.eeatrgeiaedegAmptce6irrsaiseieon0e.,eipp%(ttaldammsFsyeromilniousafrnogawpootptkrfrueiirureiegeacdrntecnrrtalheecghietttlaeeeia1aoeteongsr)hmnd(esftteiFerhg,rpnwndoeuiamnogtaeuarogssartcuegnrasmttbacfkoreuktodeaee;edrilocrpneninai1onfstptltltg)omhkwrrddiohnsoeeeteeufohdsavgwcteocosreerataaukenidtodbdnngoareleetcecfoatihicoseeomnltt;yoessrrufdkiemtreunaideestl tothietrsatpheeuratipc epuottiecnptioatleanntdiatlraanddititornaadlituisoen[a8l–u1s0e]. [8,9,10].

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